Traumatic brain injury (TBI) is a major public health concern in the US, and the current prevalence of TBI in the US is unprecedented. Individuals with TBI experience diverse patterns of early recovery and long- term clinical outcomes, and some TBI survivors experience accelerated cognitive and health decline as they age. Little is known about factors that predict different trajectories of outcome. The extent to which factors associated with cognitive and health decline in older adults in general (e.g., physical inactivity, medical comorbidity) applies to older adults with a history of TBI is not known. Many existing studies face methodological challenges that limit their usefulness in evaluating cognitive and health outcomes over time, such as small sample sizes, limited follow-up, use of imprecise functional measures, and application of traditional regression approaches whose assumptions are typically not met in longitudinal clinical studies. Our current knowledge of TBI outcomes is confined by these limitations. Recent methodological developments in psychometrics and statistical modeling can be applied to existing data sets, as proposed here, to significantly advance understanding of TBI outcomes and the factors that influence these outcomes over time. The proposed research and career development plan will first evaluate and account for measurement imprecision in commonly used TBI outcome measures, and then evaluate trajectories of temporal change in cognitive and health outcomes for individuals with TBI using advanced statistical methods ideally suited to this purpose. The research and career development plan outlined in this application consists of four complementary objectives that will be implemented during the award period. Objective 1 aims to develop proficiency in the application of advanced psychometric methods to evaluate and adjust for measurement error and bias in commonly used TBI assessment tools. Objective 2 is to acquire mastery in applying sophisticated statistical methods that are capable of evaluating longitudinal relationships among factors that influence TBI outcomes over time, and relate individual clinical trajectories to postmortem neuropathological features of TBI. Objective 3 involves establishing broad fluency in related disciplines of neuropathology, neuroimaging, and genetics that are necessary for interdisciplinary TBI research. Objective 4 is to secure independent research funding. Results from the research related to this K01 award will advance knowledge regarding potentially modifiable factors that are associated with heterogeneity in clinical outcomes over time after TBI, paving the way for appropriately timed and individually tailored interventions throughout the lifespan for TBI survivors. The knowledge gained can direct efforts to improve health and life quality for TBI survivors, and to help patients, families, and care systems plan for the future.